Each dose (0.8 ml) contains:

Gentamicin sulfate equivalent to 6880 IU gentamicin

Posaconazole 2.08 mg

Mometasone furoate monohydrate equivalent to 1.68 mg mometasone furoate

For the full list of excipients, see section ‘’Pharmaceutical particulars’’.

Ear drops, suspension.

White to off-white, viscous suspension.

Dogs

Treatment of acute otitis externa or acute exacerbation of recurrent otitis externa caused by mixed bacterial and fungal infections with Staphylococcus pseudintermedius susceptible to gentamicin and Malassezia pachydermatis susceptible to posaconazole.

Do not use in cases of hypersensitivity to the active substances or to any of the excipients, to corticosteroids, to other azole antifungal agents and to other aminoglycosides.

Do not use if the eardrum is perforated.

Do not use in pregnant or breeding animals.

Do not use concurrently with substances known to cause ototoxicity.

Do not use in dogs with generalised demodicosis.

Antimicrobial activity can be reduced by low pH and the presence of purulent and/or inflammatory debris. Ears must be cleaned before administration of the veterinary medicinal product. Compatibility with ear cleaners has not been demonstrated.

Bacterial and fungal otitis is often secondary to other conditions. In animals with a history of recurrent otitis externa, the underlying causes of the condition such as allergy or anatomical conformation of the ear must be addressed in order to avoid ineffective treatment with a veterinary medicinal product. Efficacy of this veterinary medicinal product was not assessed in dogs with atopic or allergic skin conditions.

Cross-resistance between gentamicin and other members of the aminoglycoside class has been shown in Staphylococcus pseudintermedius. Use of the product should be carefully considered when susceptibility testing has shown resistance to aminoglycosides because its effectiveness may be reduced. Co-selection for other classes of antimicrobials is common.

The safety of the product has not been established in dogs less than 3 months of age or weighing less than 3 kg.

Before the veterinary medicinal product is applied, the external auditory canal must be examined thoroughly to ensure that the eardrum is not perforated, in order to avoid the risk of transmission of the infection to the middle ear and to prevent damage to the cochlear and vestibular apparatus.

Re-evaluate the dog immediately if worsening of clinical signs, hearing loss or signs of vestibular dysfunction are observed during treatment or if the dog is not showing signs of improvement by day 14.

Cytology of ear canal is recommended prior to the use of the product to identify a mixed infection.

This antimicrobial combination should only be used where diagnostic testing has indicated the need for simultaneous administration of each of the active substances.

Use of the product should be based on identification and susceptibility testing of the target pathogens. Ideally, therapy should be based on epidemiological information and knowledge of susceptibility of the target pathogens at local/regional level.

Use of the product should be in accordance with official, national and regional antimicrobial policies.

If hypersensitivity to any of the components occurs, treatment should be discontinued and appropriate therapy instituted.

In case of parasitic otitis, an appropriate acaricidal treatment should be implemented.

Prolonged and intensive use of topical corticosteroids preparation is known to trigger systemic effects, including suppression of adrenal function.

Use with precaution in dogs with suspected or confirmed endocrine disorder (i.e. diabetes mellitus; hypo-thyroid disease, etc).

Ototoxicity may be associated with gentamicin treatment. Experience shows that geriatric dogs are more at risk of hearing impairment after topical ear product administration.

Objective hearing assessments were not performed in the pivotal field trial. Dogs with signs of impaired balance or loss of hearing after administration should be re-examined.

The veterinary medicinal product may be slightly irritating to eyes. Accidental eye exposure may occur when the dog shakes its head during or just after administration. In case of accidental eye contact, flush the eyes thoroughly with water for 15 minutes. If symptoms develop, seek medical advice and show the package leaflet or the label to a physician.

Although no potential for skin irritation was indicated by experimental studies, contact of the product with the skin should be avoided. In case of accidental skin contact, wash the exposed skin with water.

Close contact between the dog and children should be limited in the days following the treatment due to unknown amount of the product possibly leaking from treated ear/s.

The product may be harmful after ingestion. Avoid ingestion of the product including hand-to-mouth exposure. In case of accidental ingestion, seek medical advice immediately and show the package leaflet or the label to the physician.

No adverse reactions related to treatment were observed in clinical trials.

The safety of the veterinary medicinal product has not been established during pregnancy and lactation. Do not use during pregnancy and lactation.

Studies to determine the effect on fertility in dogs have not been conducted. Do not use in breeding animals.

None known.

Auricular use.

Single treatment.

The recommended dosage is a single dose of 0.8 ml per infected ear.

The maximum clinical response may not be seen until 28 to 42 days after administration.

Instructions for use:

The product should be administered only by veterinarians or by trained personnel under close veterinary supervision.

Clean and dry the external ear canal before administering the product.

The product is preservative-free and should be handled using clean technique.

Before first use, shake the bottle vigorously for 15 seconds. Unwrap the syringe with the adapter attached. Remove the cap from the bottle and insert the adapter by pressing it firmly into the top of the bottle using the attached syringe. Follow steps 1. to 5. of the dosing instructions.

Use a new syringe for each infected ear. Shake the bottle vigorously for 15 seconds before use. Remove the cap. Insert the syringe tip into the adapter. Follow steps 1. to 5. of the dosing instructions.

Dosing syringes compatible with the syringe adapter are provided. Some commercially available syringes may not be compatible with the syringe adapter.

Do not clean the ear canal for at least 28 days after the administration to allow contact of the product with the ear canal.

Auricular administration to puppies at up to 5 times the recommended dose to both ears on 3 occasions at 2-week intervals was evaluated in a target animals safety study.

All findings were consistent with glucocorticoid administration. Findings in the 3X and 5X overdose groups included mild eosinopenia, lower baseline and ACTH-induced cortisol levels, lower mean adrenal weights with correlating minimal to mild atrophy of the adrenal cortex. Minimal to mild atrophy of the epidermis of the external auditory canal and the epithelial lining of the external surface of the tympanic membrane was observed in the 1X, 3X and 5X groups, consistent with the pharmacological effects of glucocorticoids and known to be reversible after cessation of treatment. ACTH administration at the end of the study elicited an increase in cortisol levels in all study groups, indicative of sufficient adrenal function.

All findings were of low severity, are considered reversible after cessation of treatment, and were not associated with clinical signs or hearing effects.

Not applicable.

ATCvet code: QS02CA91

Otologicals – Corticosteroids and anti-infectives in combination.

The veterinary medicinal product is a fixed combination of three active substances (antibiotic, antifungal and corticosteroid).

Gentamicin is an aminoglycoside bactericidal, concentration dependent antibiotic which acts by inhibiting protein synthesis. Its spectrum of activity includes Gram-positive and Gram-negative bacteria, such as the following pathogenic organism isolated from the ears of dogs: Staphylococcus pseudintermedius.

Bacterial resistance to aminoglycosides can be mediated by aminoglycoside modifying enzymes, such as acetyltransferases, phosphotransferases and nucleotidyltransferases, by reduced drug uptake or active efflux mechanisms and by target modification, such as 16S rRNA methylation. Aminoglycoside resistance determinants are often located on mobile genetic elements.

Posaconazole is a broad-spectrum triazole antifungal agent. The mechanism by which posaconazole exerts fungicidal action involves the selective inhibition of the enzyme lanosterol 14-demethylase (CYP51) involved in ergosterol biosynthesis in yeasts and filamentous fungi. In in vitro tests, posaconazole has shown fungicidal activity against most of the approximately 7,000 strains of yeast and filamentous fungi tested. Posaconazole is 40 – 100 times more potent in vitro against Malassezia pachydermatis than clotrimazole, miconazole nystatin and terbinafine.

The most common mechanisms of resistance to azoles in clinical isolates are alterations in lanosterol 14α-demethylase biosynthesis (e.g. by mutations), increased production of this enzyme or increased efflux (e.g. by ABC transporters or major facilitators). Posaconazole is not an MDR1 major facilitator substrate.

Mometasone furoate is a corticosteroid with high topical potency, but few systemic effects. Like other topical corticosteroids, it has anti-inflammatory and anti-pruritic properties.

Table 1: Minimum Inhibitory Concentration (MIC) range, MIC50 and MIC90 of gentamicin determined for Staphylococcus

Table 2: MIC range, MIC50 and MIC90 of posaconazole determined for Malassezia pachydermatis isolates (n=50).

All isolates, collected from dogs between 2017 and 2020 in different European countries, were epidemiologically unrelated.

Systemic absorption and depletion from the ear wax of the three active substances was determined after a single administration of the recommended dose into both ear canals of healthy beagle dogs. Plasma and ear wax concentrations were measured at 1, 7, 14, 21, 30, and 45-days post-administration.

Systemic exposure was only detected at 1-day post-administration with low plasma concentrations (≤ 7.9 ng/ml) of gentamicin and posaconazole. At 14 days and 45 days post-administration, only one dog was found to have a detectable amount of gentamicin and posaconazole in the plasma, respectively. Plasma concentrations for all other time points for gentamicin and posaconazole were below the limit of quantification. Plasma concentrations of mometasone furoate were below the limit of quantification at every time point.

Gentamicin, posaconazole, and mometasone furoate were detected in ear wax throughout the 45-day study with depletion occurring progressively from days 1 to 45, and levels remaining detectable until day 45.

Paraffin liquid

Plasticized hydrocarbon gel (polyethylene, mineral oil)

None known.

Shelf life of the veterinary medicinal product as packaged for sale: 2 years.

Shelf life after first opening the immediate packaging: 3 months.

This veterinary medicinal product does not require any special storage conditions.

White high-density polyethylene (HDPE) bottle with a white low-density polyethylene (LDPE) screw cap. 20 polypropylene syringes of 1.0 ml capacity one with a LDPE press-in bottle adapter attached. One bottle contains 16 ml of product, corresponding to 20 doses of 0.8 ml.

Carton box containing 1 bottle, an LDPE adaptor and 20 syringes.

Any unused veterinary medicinal product or waste materials derived from such veterinary medicinal product should be disposed of in accordance with local requirements.

UK(GB): Vm 01708/5062

17 February 2023

Not applicable.

For animal treatment only.

Keep out of the sight and reach of children.

Administration by a veterinary surgeon or under their close supervision.